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Synthesis of 99mTc-p-SCN-Bzl-TCMC-bevacizumab for vascular endothelial growth factor (VEGF) receptor imaging using ovarian cancer model

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Abstract

In this study bevacizumab was labeled with 99mTc using p-SCN-Bzl-TCMC as a chelator for non invasive imaging of VEGF receptor in ovarian tumor Sprague Dawley rat and New Zealand rabbit models. High radiochemical purity and stability were observed using 0.4 mL of conjugated TCMC-bevacizumab. In vitro binding studies showed higher uptake of labeled conjugated bevacizumab with high metastatic SKOV-3 ipl cells as compared to poor metastatic SKOV-3. Biodistribution in rat model confirmed higher accumulation of labeled conjugated bevacizumab in the site infected with SKOV-3 ipl cells as compared to SKOV-3. Images of ovarian tumor rabbit model validated its specificity and efficacy as a promising ovarian tumor imaging agent.

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References

  1. Wang Y, Wang L, Chen C, Chu X (2018) New insights into the regulatory role of microRNA in tumor angiogenesis and clinical implications. Mol Cancer 17:22–31

    Article  Google Scholar 

  2. Rajabi M, Mousa S (2017) The role of angiogenesis in cancer treatment. Biomedicines 5:34–45

    Article  Google Scholar 

  3. Elshabrawy HA, Chen Z, Volin MV, Ravella S, Virupannavar S, Shahrara S (2015) The pathogenic role of angiogenesis in rheumatoid arthritis. Angiogenesis 18:433–448

    Article  CAS  Google Scholar 

  4. Mashreghi M, Azarpara H, Bazaz MR, Jafari A, Masoudifar A, Mirzaei H, Jaafari MR (2018) Angiogenesis biomarkers and their targeting ligands as potential targets for tumor angiogenesis. J Cell Physiol 233:2949–2965

    Article  CAS  Google Scholar 

  5. Rahmathulla G, Hovey EJ, Hashemi-Sadraei N, Ahluwalia MS (2013) Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges. Onco Targets Ther 6:371–389

    Article  CAS  Google Scholar 

  6. Wagner J, Kline CL, Zhou L, Khazak V, El-Deiry WS (2018) Anti-tumor effects of ONC201 in combination with VEGF-inhibitors significantly impacts colorectal cancer growth and survival in vivo through complementary non-overlapping mechanisms. J Exp Clin Cancer Res 37:11–22

    Article  Google Scholar 

  7. Murukesh N, Dive C, Jayson GC (2010) Biomarkers of angiogenesis and their role in the development of VEGF inhibitors. Br J Cancer 102:8–18

    Article  CAS  Google Scholar 

  8. Yu Y, Chen R, Sun Y, Pan Y, Tang W, Zhang S, Cao L, Yuan Y, Wang J, Liu C (2018) Manipulation of VEGF-induced angiogenesis by 2-N, 6-O-sulfated chitosan. Acta Biomater 71:510–521

    Article  CAS  Google Scholar 

  9. Muratori L, Gnavi S, Fregnan F, Mancardi A, Raimondo S, Perroteau I, Geuna S (2018) Evaluation of vascular endothelial growth factor (vegf) and its family member expression after peripheral nerve regeneration and denervation. Anat Rec 301:646–1656

    Article  Google Scholar 

  10. Peach C, Mignone V, Arruda M, Alcobia D, Hill S, Kilpatrick L, Woolard J (2018) Molecular pharmacology of VEGF-A isoforms: binding and signalling at VEGFR2. Int J Mol Sci 19:1264–1291

    Article  Google Scholar 

  11. Mahase S, Rattenni RN, Wesseling P, Leenders W, Baldotto C, Jain R, Zagzag D (2017) Hypoxia-mediated mechanisms associated with antiangiogenic treatment resistance in glioblastomas. Am J Pathol 187:940–953

    Article  CAS  Google Scholar 

  12. Viallard C, Larrivee B (2017) Tumor angiogenesis and vascular normalization: alternative therapeutic targets. Angiogenesis 20:409–426

    Article  CAS  Google Scholar 

  13. Lin R, Huang J, Wang L, Li Y, Lipowska M, Wu H, Yang J, Mao H (2018) Bevacizumab and near infrared probe conjugated iron oxide nanoparticles for vascular endothelial growth factor targeted MR and optical imaging. Biomater Sci 6:1517–1525

    Article  CAS  Google Scholar 

  14. Atzori MG, Tentori L, Ruffini F, Ceci C, Bonanno E, Scimeca M, Lacal PM, Graziani G (2018) The anti-vascular endothelial growth factor receptor-1 monoclonal antibody D16F7 inhibits giloma growth and angiogenesis in vivo. J Pharmacol Exp Ther 364:77–86

    Article  CAS  Google Scholar 

  15. Cecchini A, Raffa V, Canfarotta F, Signore G, Piletsky S, MacDonald MP, Cuschieri A (2017) In vivo recognition of human vascular endothelial growth factor by molecularly imprinted polymers. Nano Lett 17:2307–2312

    Article  CAS  Google Scholar 

  16. Eryılmaz MK, Mutlu H, Yalçin MF, Salim DK, Tazegul G, Coskun HS (2017) Severe periocular bleeding induced by bevacizumab in a patient with recurrent glioblastoma multiforme. J Oncol Pharm Pract 23:392–395

    Article  Google Scholar 

  17. Aalders KC, Tryfonidis K, Senkus E, Cardos F (2017) Anti-angiogenic treatment in breast cancer: facts, successes, failures and future perspectives. Cancer Treat Rev 53:98–100

    Article  CAS  Google Scholar 

  18. Dorff TB, Longmate JA, Pal SK, Stadler WM, Fishman MN, Vaishampayan UN, Rao A, Pinksi JK, Hu JS, Quinn DI (2017) Bevacizumab alone or in combination with trc105 for patients with refractory metastatic renal cell cancer. Cancer 123:4566–4573

    Article  CAS  Google Scholar 

  19. Zhang W, Shen Z, Luo H, Hu X, Zheng L, Zhu X (2017) The benefits and side effects of bevacizumab in the treatment of recurrent ovarian cancer. Curr Drug Targets 18:1125–1131

    CAS  PubMed  Google Scholar 

  20. Zhao S, Gao F, Zhang Y, Zhang Z, Zhang L (2018) Bevacizumab in combination with different platinum-based doublets in the first-line treatment for advanced non squamous non-small-cell lung cancer: a network meta-analysis. Int J Cancer 142:1676–1688

    Article  CAS  Google Scholar 

  21. Shord SS, Bressler LR, Tierney LA, Cuellar S, George A (2009) Understanding and managing the possible adverse effects associated with bevacizumab. Am J Health Syst Pharm 66:999–1013

    Article  CAS  Google Scholar 

  22. Mather SJ, Ellison D (1990) Reduction-mediated technetium-99m labeling of monoclonal antibodies. J Nucl Med 31:692–697

    CAS  PubMed  Google Scholar 

  23. Boros E, Holland JP (2018) Chemical aspects of metal ion chelation in the synthesis and application antibody-based radiotracers. J Label Compd Radiopharm 61:652–671

    Article  CAS  Google Scholar 

  24. Yudistiro R, Hanaoka H, Katsumata N, Yamaguchi A, Tsushima Y (2018) Bevacizumab radioimmunotherapy (RIT) with accelerated blood clearance using the Avidin Chase. Mol Pharmaceutics 15:2165–2173

    Article  CAS  Google Scholar 

  25. Meredith RF, Torgue J, Azure MT, Shen S, Saddekni S, Banaga E, Carlise R, Bunch P, Yoder D, Alvarez R (2014) Pharmacokinetics and imaging of 212Pb-TCMC-trastuzumab after intraperitoneal administration in ovarian cancer patients. Cancer Biother Radiopharm 29:12–17

    Article  CAS  Google Scholar 

  26. Chappell LL, Dadachova E, Milenic DE, Garmestani K, Wu C, Brechbiel MW (2000) Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes 203Pb and 212Pb. Nucl Med Biol 27:93–100

    Article  CAS  Google Scholar 

  27. Milenic DE, Molinolo AA, Solivella MS, Banaga E, Torgue J, Besnainou S, Brechbiel MW, Baidoo KE (2015) Toxicological studies of 212Pb intravenously or intraperitoneally injected into mice for a phase 1 trial. Pharmaceuticals 8:416–434

    Article  CAS  Google Scholar 

  28. Shah SQ, Mahmood S (2018) Evaluation of 99mTc-labeled bevacizumab-N-H, YNIC conjugate in human ovarian tumor xenografts. Cancer Biother Radiopharm 33:96–102

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Biochemistry Section, Institute of Chemical Sciences, University of Peshawar, K.P.K, Peshawar, 25120, Pakistan

    Bibi Faiza & Syed Qaiser Shah

Authors
  1. Bibi Faiza
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  2. Syed Qaiser Shah
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Contributions

FB performed conjugation of Bevacizumab with p-SCN-Bzl-TCMC, labeling with radionuclide, in vitro studies and biodistribution in animal model rats. SS performed the imaging studies using model rabbit. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Bibi Faiza.

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No conflict/competing interests.

Ethics approval

Approval for experiments on rats and rabbits models was obtained from Ethics Committee of Faculty of Life and Environmental Sciences (FLES) University of Peshawar (No. 154/EC/LIFE). The procedures used in this study adhere to the tenets of the Animal (Scientific Procedure) Act 1986.

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Faiza, B., Shah, S.Q. Synthesis of 99mTc-p-SCN-Bzl-TCMC-bevacizumab for vascular endothelial growth factor (VEGF) receptor imaging using ovarian cancer model. J Radioanal Nucl Chem 325, 147–154 (2020). https://doi.org/10.1007/s10967-020-07202-9

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  • DOI: https://doi.org/10.1007/s10967-020-07202-9

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